Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics-pharmacodynamics study in rhesus monkeys following intramuscular administration.
OBJECTIVE
Investigation into pharmacokinetic-pharmacodynamic properties of interferon- alpha (IFN-alpha)2b-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) in rhesus monkey primates.


METHODS
IFN-alpha2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys (n=3) were injected intramuscularly with either 3 MIU/kg commercial IFN-alpha2b lyophilized powder or IFN-alpha2b-loaded PLGA microspheres (inherent viscosity of 0.89 dL/g). In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay (ELISA) method to evaluate biological activity of the microspheres in rhesus monkeys.


RESULTS
The IFN-alpha2b microspheres with 3 inherent viscosities (0.39, 0.89, and 1.13 dL/g) were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 microm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-alpha2b microspheres and IFN-alpha2b lyophilized powder were significantly different (P<0.05).


CONCLUSIONS
The drug residence time for the IFN-alpha2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.
Zhang
Yong-ming
YM
State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, College of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Yang
Fan
F
Yang
Yi-qun
YQ
Song
Feng-lan
FL
Xu
An-long
AL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D005079:Excipients; D007273:Injections, Intramuscular; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019344:Lactic Acid; D008253:Macaca mulatta; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid